Finding a Potential Dipeptidyl Peptidase-4 (DPP-4) Inhibitor for Type-2 Diabetes Treatment Based on Molecular Docking, Pharmacophore Generation, and Molecular Dynamics Simulation

Abstract BackgroundAlthough the clinical effect of stir-fried Dolichos lablab L. kernel has been approved in modern traditional Chinese medicine, existing associated studies mainly focus on its clinical studies and chemical ingredients. However, there are few studies on pharmacodynamics material basis and molecular mechanism of stirfried Dolichos lablab L. kernel in treatment of type-2 diabetes(T2DM), thus restricting the further development and utilization of stir-fried Dolichos lablab L. kernel.MethodsA qualitative analysis on saponin chemical ingredients of stir-fried Dolichos lablab L. kernel was performed using UHPLC-Q-Exactive Orbitrap MS. A total of 10 saponin ingredients were selected. Moreover, target screening, biological process and metabolism pathway analysis were accomplished by network pharmacology. Four key proteins(EGFR, IGF1, MAPK1 and PIK3R1) of type-2 diabetes were selected for molecular docking verification with saponin ingredients. Specifically, molecular dynamics simulation of ingredients which have strong bindings with proteins was conducted. ResultsIn this study, 16 saponin ingredients were identified from stir-fried Dolichos lablab L. kernel. There were 91 intersection targets and the KEGG pathway enrichment involved 20 relevant pathways. According to the molecular docking verification, saponin ingredients of stir-fried Dolichos lablab L. kernel can form stable binding with key protein targets. The molecular dynamics simulation further verifies stability and reasonability of the docking results. ConclusionsThis study provides references to identification of efficient ingredients of stir-fried Dolichos lablab L. kernel, screening of quality markers and explanation of relevant action mechanism by combining UHPLC-Q-Exactive Orbitrap MS and network pharmacology.

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Design, synthesis, biological evaluation and molecular dynamics simulation studies of (R)-5-methylthiazolidin-4-One derivatives as megakaryocyte protein tyrosine phosphatase 2 (PTP-MEG2) inhibitors for the treatment of type 2 diabetes

Journal of Biomolecular Structure and Dynamics ◽

10.1080/07391102.2019.1654410 ◽

2019 ◽

Vol 38 (11) ◽

pp. 3156-3165 ◽

Cited By ~ 3

Author(s):

Jingwei Wu ◽

Yingzhan Sun ◽

Hui Zhou ◽

Ying Ma ◽

Runling Wang

Keyword(s):

Type 2 Diabetes ◽

Molecular Dynamics ◽

Molecular Dynamics Simulation ◽

Protein Tyrosine Phosphatase ◽

Tyrosine Phosphatase ◽

Biological Evaluation ◽

Dynamics Simulation ◽

Simulation Studies ◽

Design Synthesis

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Exploring the Therapeutic Ability of Fenugreek against Type 2 Diabetes and Breast Cancer Employing Molecular Docking and Molecular Dynamics Simulations

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2018/1943203 ◽

2018 ◽

Vol 2018 ◽

pp. 1-12 ◽

Cited By ~ 3

Author(s):

Shailima Rampogu ◽

Saravanan Parameswaran ◽

Mary Rampogu Lemuel ◽

Keun Woo Lee

Keyword(s):

Breast Cancer ◽

Type 2 Diabetes ◽

Molecular Dynamics ◽

Molecular Docking ◽

Md Simulations ◽

Dynamics Simulation ◽

Drug Candidate ◽

Phytochemical Analysis ◽

Fenugreek Seed

Fenugreek (Trigonella foenum-graecum) is used as a spice throughout the world. It is known for its medicinal properties such as antidiabetic, anticarcinogenic, and immunological activities. The present study shows the properties and the nutritional quality of fenugreek seed extract and focuses on screening of active compounds in drug designing for type 2 diabetes and breast cancer. Quantitative analysis was used to calculate the percentages of protein, carbohydrates moisture, fatty acid, galactomannan, oil, and amino acid. Phytochemical analysis revealed the presence of flavonoids, terpenoids, phenols, proteins, saponins, and tannins in fenugreek seed extracts. Molecular docking and molecular dynamics simulation-based computational drug discovery methods were employed to address the role of fenugreek seed constituents against type 2 diabetes and breast cancer. The computational results reveal that the compound galactomannan can be ascribed as potential drug candidate against breast cancer and type 2 diabetes rendered by higher molecular dock scores, stable molecular dynamics (MD) simulations results, and lower binding energy calculations.

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Molecular understanding of GPR120 agonist binding using homology modeling and molecular dynamics

10.33774/chemrxiv-2021-s23lv ◽

2021 ◽

Author(s):

suyash pant ◽

V Ravichandiran

Keyword(s):

Type 2 Diabetes ◽

Molecular Dynamics ◽

Molecular Dynamics Simulation ◽

Homology Model ◽

Dynamics Simulation ◽

Binding Modes ◽

Promising Therapeutic Target ◽

Important Interaction ◽

To Come

The toll of type-2 diabetes and associated complications are continues, efforts to identify possible targets are ongoing. Free fatty acid receptor 4 (FFAR4/GPR120) has been recently identified to be a promising therapeutic target for a group of metabolic associated disorders. For the prevention of type 2 diabetes, significant scientific and commercial interest has been developed around GPR120 and its role. Due to the unavailability of a crystal structure, the interaction dynamics of GPR120 agonists were not yet determined to date. In the present study, we constructed the homology model for GPR120 and validated using available mutational data and molecular dynamics simulation, and explored its binding modes with known small molecule agonists. So, sixteen propionic acid derivatives as GPR120 agonists were collected to elucidate their binding modes. Experiential and theoretical studies suggested that the carboxylic group of ligands interact with Arg99, which is an important interaction for GPR120 activation. However, earlier reports also suggest that this interaction is not stable during the molecular dynamics simulation, which contradicts the experimental observations. Evidently, to refute this, we got a stable interaction of Arg99 with TUG891 and other recently reported 15 GPR120 agonists. In addition, we have also observed that in 1 µs molecular dynamics simulation Arg183 present in ECL2 tends to come inside and interact with ligand. Molecular dynamics simulation study provides a list of key hotspot residues which play an important role in ligand binding. The homology model and results provides could be further utilized as a powerful template to accelerate the research in this field.

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